Attacking Pain on all Fronts - PowerPoint Presentation

Attacking Pain on all Fronts Edward C. Covington, M.D.

Why a Symposium on Pain? It’s difficult Many treatments, none fully effective Patients suffer unnecessarilyOptimal treatment requires A combination of interventionsA cohesive team of diverse professionsClose coordination with the patient

Between the Bookends Research Focus: Acute pain Trauma, surgery, acute illnessChronic painMonths, years duration, often little explanation Management often differs dramatically e.g., 5 hours vs 5 years after multi-level lumbar fusion There is no switch – acute evolves into chronic

Prevalence of Pain Outpatients Representative sample – 27,035 US adultsPoint-prevalence of chronic pain:30.7% Half of those had daily painAverage intensity was severe ≥ 7/10 Johannes CB et al. J Pain 2010;11(11):1230-1239. Inpatients Self-report, 10 screening days N = 602 medical and (elective) surgical admissions in OsloSevere pain (NRS ≥ 7)22% of surgical patients18% of medical patientsLudvigsen ES et al. J Clin Nurs. 2016 Jun 7. [Epub ahead of print]

Importance of Inpatient Pain Relief of suffering Consequences of undertreated pain Increased LOSPulmonary complicationsDelayed functional rehabilitationCatananti, Gambassi . Surg Oncol 2010; 19, 140-148. Herr K. J Pain 2011; 12, S3-S13. Prospective cohort study N = 411 with hip fracture Higher postop pain leads to: Chronic functional impairmentLonger lengths of stay More missed PT sessionsLower locomotion scores at 6 monthsMorrison RS, Pain 2003; 103: 303-311Numerous authors state poor treatment of acute pain leads to chronic pain More accurate to say unrelieved acute pain correlates with persistent pain Causation unclear Kehlet H et al. Lancet 2006;367:1618-1625 . Pre-emptive / prevention strategies may reduce persistent pain Katz & Seltzer. Expert Rev Neurother . 2009;9(5):723-44.

Progress The last 40 years Major insights into pain physiology Increased workplace safetyImproved work access for the disabledAmericans with Disabilities ActNew treatmentsSurgeries (e.g. disc replacement)Neuroaugmentation Nerve blocks Antihyperalgesic medications Liberalization of chronic opioid rx Results: The rate of disability doubles every 15 years Most of it pain related

Inpatient Pain Management Has Improved 441 mixed surgical inpatients Questionnaires 2015, identical to 2003 studyQuestionnaires before discharge Phone f/u 1 and 2 weeks later Discharge:12% “ Severe-to-Extreme” pain 54% “ Moderate-to-Extreme” pain During first 2 weeks after discharge13% had “Severe-to-Extreme” pain 46% had “Moderate to-Extreme” painInappropriate to statistically compare results with retrospective 2003 survey, but … Severe-extreme pain postop35% in 2003 vs 12% in 2015Severe-extreme 1st 2 wks 22 % in 2003 vs 13% now. Buvanendran A et al. Pain Medicine 2015; 16: 2277–2283 .Apfelbaum JL, et al. Anesth Analg 2003;97(2):534­40. Pain at Discharge Frequency (%) None Slight Mod Severe Extreme Verbal Pain Scale

But Not Enough Despite improvements, there remain serious deficits in assessment and intervention for inpatient pain Providers tend to underestimate pain needsUnder-treat in general For older people in particular (Review) Prowse M. J Clin Nurs 2007;16(1):84-97 .

Pain Primer – A Biopsychosocial Condition Neurobiology Psychology Environment Biopsychosocial Model

Pain Pathway – Descartes (1664) Straight wire Now with synapses Stimulus magnitude determines Signal strength Cortical response Pain appreciation No fire – no pain Melzack R, Wall PD: Pain mechanisms: a new theory. Science, 150:971, 1965. Medical School (1970) Synapse

Problems with Descartes Straight wire concept wrongly implies fixed stimulus : pain relationship. Pain is more a creation of the nervous system than a gauge of stimulus intensity. Pain changes the nervous system. Failure to explain pain may result not from looking in the wrong place , but from looking at the wrong time – the cause may be in the past. Effective treatment of acute pain may be essential to prevent development of chronic pain .

Transduction: Primary Afferent fibers CGRP: Calcitonin gene-related peptide. DRG: Dorsal root ganglion. NGF: Nerve growth factor. SP: Substance P. TG: Trigeminal ganglion. TRP: Transient receptor potential. ASIC: Acid sensing ion channel. TREK:TWIK-1-related K + Julius D, Basbaum AI. Nature . 2001;413:203 − 210. Noxious stimuli activate specific molecular transducers Pain Spinal dorsal horn neurons/ nucleus caudalis MDEG DRASIC TREK-1 Mechanical TRPV1 ASIC DRASIC Acid DRG/TG Neurotransmitter release (CGRP, Glutamate, SP) TRPM8 Cold TRPV1 TRPV2 TRPV3 Heat

So WhyDo you ache all over when you have the flu? Do people in heroin withdrawal have bone / muscle pain?

Scientific American Medicine Nociceptors: Free nerve endings Contain receptors for BK, 5-HT, PGE 2 , ATP, H + Orientation Pain: A , C

Descending Pain Facilitation / Inhibition Rostral Ventromedial Medulla (nucleus raphe magnus) On cells excite pain receptors Off cells inhibit pain receptors Opioids disinhibit off cells, inhibit on cells May generate pain without peripheral stimulus Tasks requiring attention to nociception or to visual cues cause activation of on cells prior to pain stimulus During opioid abstinence, on-cell firing markedly increases Fields HL, et al. J Neurophysiol . 1995 Opioid Opioid

LorraineWhat happened to her pain when she had to go a night without her accustomed opioids? Similar to patients switched from PCA to much lower dose prns at discharge

Descending Modulation of Pain Attention, expectations, excitement modulate pain Electrical / opioid stimulation of DLF  analgesia Activation pain, fear, acupuncture, counter-irritation, antidepressants Analgesia antagonized by 5-HT and NE antagonists De Felice M et al. Pain 2011;152:2701–9

LA BLA CeA Nociceptive amygdala Polymodal Cortex Thalamus Brainstem Spinal cord Amygdala – Inputs Nociceptive information from cord and brainstem Processed information from the thalamus and cortex Integrates information Attaches significance to painful stimuli. Neugebauer V et al. Neuroscientist 2004;10(3):221-234 Nociceptive

LA BLA CeA Nociceptive amygdala Thalamus Cortex conscious cognitive Brainstem Spinal cord Expression modulation Autonomic endocrine hypothalamus Amygdala – Outputs Connections with forebrain and brainstem Projections to thalamus and cortex may be related to cognitive and conscious components of pain. Autonomic and endocrine pain responses via hypothalamus Emotional expression and modulation of pain regulated via projections to brainstem pain-modulating system Neugebauer V et al. Neuroscientist 2004;10(3):221-234

Functional MRI vs. Subjective Pain Pain intensity ratings During functional MRI 49°C stimulusCoghill RC et al. PNAS 2003 median

High subjective pain Low subjective pain Primary somatosensory cortex Prefrontal cortex Coghill RC et al. Proc Nat Acad Sci 2003 Anterior cingulate

Implications Pain is what the patient says it is. When incentives removed from the situation “Unexplained pain” ≠ “psychogenic” Genetic?

The CNS Has Limited Bandwidth It can’t perceive / process the infinity of things around it. Kids “don’t hear” when absorbed in a video game You close your eyes to hear a faint soundHow does it “decide” what to process?

Bushnell M. C. et.al. PNAS 1999;96:7705-7709 Attention to Pain Modulates S1 Activity Pain-related activity Attention directed to painful heat stimulus (Left) Or to auditory stimulus (Right)

LorraineHow does it “decide” what to process? Salience – We notice what matters most. Pain that means I spent too much time lying around and became weak Pain that means the cancer’s back

Afferent fibers C fiber A- β fiber Nerve injury Phenotypic Changes Spinal cord Neuroplasticity Central sensitization Alteration of modulatory systems Ectopic discharge Sensitization Woolf & Mannion , Lancet 1999 Attal & Bouhassira , Acta Neurol Scand 1999 Evolving Changes with Nerve Injury Demyelination Regeneration Perineural inflammation

Pain Is the Disease Nerve injury sensitizes Dorsal horn sensitizes Thalamus sensitizes Cortex Thus:Chronic pain is not simply acute pain that persistedIt is a different phenomenon neurophysiologicallyThe longer it lasts, the more central / less peripheral it is Evolving pathology:

Lorraine Distal paresthesias Often become painful There is no stimulusTreatment?Central pain doesn’t respond to treating nociception (e.g. NSAIDs)

The Disease Psychological Influences on Pain The attention in pain medicine Pathophysiology Pharmacology Interventions Results of treatment “30% improvement at 1 year” Opioids, anti-epileptics, antidepressants, intrathecal therapies Many remain miserable, dysfunctionalThe key, often, is the psyche The Usual Focus

Critical Psychological Issues in Pain and Disability Pathogenic cognitions SelfConditionOthers Fear Incentives Personality Psychiatric illness Depression Anxiety AddictionSomatization

Primary Ways the Psyche Impacts Pain Vigilance Pain is the focus of attention Distraction is the oppositeBehavior – What they doVigilance augments pain perception Behavior determines deconditioning / disability

Abuse → Nociceptive Sensitization 10 IBS pts, 10 controls Half reported history of abuse fMRI and pain ratings obtained during rectal distentions Abuse → more pain, more activationRingel Y et al. Gastroenterology 2008;134:396–404 Abuse hx Non-abused

Cognitive Causes of Disability Fitness and education can be curative Misunderstanding , misinformation Inactivity Deconditioning Cycle of escalating pain, disability

Cognition => Pain / Behavior “Unmotivated” spine patient Lorraine’s hip?

Feelings Derive from Beliefs, Perceptions

Cognition and Pain The aversive quality of pain is modified by its interpretation Catastrophic interpretations worsen pain and hinder coping “My nerves are being crushed.”“These exercises must be tearing something loose.”

Pathogenic Cognitions – Negative Pain Mysterious Indicative of body damageSelfHelplessFragileThe worldIndifferent – hostile Without opportunity

Catastrophizing ↔ Pain Study of 538 patients with neuropathic pain Assessed catastrophizing, pain, and interference with function Followed 6 monthsEarly decreases in catastrophizing predicted improvement in pain and interference. Early reduction in pain intensity /interference predicted reduced catastrophizing. Racine M et al. Pain 2016; 157(9):1946–1953

Catastrophizing Predicts TKA Outcome Prospective: Pre-op Pain Catastrophizing ScalePost-op TKA pain, functionGreater catastrophizing predicted failure:To achieve 50% pain reduction (OR 2.67) To have ≥ 4/20 point WOMAC* pain reduction at 6 months (OR 6.04) Riddle DL et al. Clin Orthop Relat Res 2010; 468(3): 798-806.*Western Ontario and McMaster Arthritis Index Pain & Function

LorraineCatastrophizing about insurance forms and multiple appointments? Irritable and hyperalgesic due to opioid withdrawal? Is cognitive impairment unmasked by sudden loss of support / structure?

Mood Modulates Pain Mood induction by reading Tolerance to experimental pain Increased by induction of elationDiminished by induction of sadness Zelman DC, et al. Pain. 1991;46:105–111.Similar effects of hypnotically induced mood statesRainville P, et al. Pain. 2005;118:306–318.

Mood and Pain Anxiety, depression, anger N = 300 pain rehabilitation admissionsProfile of Mood StatesRatings > moderateCovington EC, unpublished

Pre-op Distress – Post-op Status Meta-Analysis 47 studies, 6,207 patientsPreop emotional distress predictedPostop painAnalgesic useImpairment Effect sizes larger in studies that assessed catastrophizing, anxiety, and depression Jackson T et al. J  Pain. 2016;17(8):874-88.

Mood Effects Consistent Across Types of Surgery N = 120 gastric bypass (bariatric) patientsPostop pain, PCA use predicted by pre-op depression and anxiety Aceto P et al. Physiol Behav. 2016;163:1-6 . N = 82, ENT surgery Postop pain higher if high depression, anxiety scores Severe pain predicted by pre-op depressionSuffeda A et al. Medicine (Baltimore). 2016;95(28):e4256.

Depression and Pain Mutually Reinforcing N = 483 neurology outpatients Followed 12 mo Depression severity at f/u predicted byBaseline depressionBaseline pain Lack of pain improvement Pain severity at follow-up predicted by Baseline pain Baseline depression Lack of depression improvement Conclusion: Pain is more persistent in depression, and vice versa Williams L et al. Neurology. 2004.

Anxiety Predicts Chronification of Trauma Pain N = 205, hospitalized for musculoskeletal injuryData collected in hospital and at 4 mo32% had moderate-severe neuropathic pain at 4 monthsPredictors Elevated general anxiety in-hospital Symptoms of posttraumatic stress at 4 months Rosenbloom BN et al. Pain. 2016;157(8):1733-43..

PTSD → More Pain, More Inflammation Pain Intensity Capsaicin injection into quadriceps PTSD vs controls More reported pain Higher secret ion of pro-inflammatory cytokine IL-1 into CSFDelayed release of anti-inflammatory cytokine IL-10.Lerman I et al. Psychoneuroendocrinology. 2016;73:99-108. Minutes Post-Injection

Lorraine If her depression is inadequately treated (Duloxetine 20 is usually inadequate) Her recovery will be impededPain worseExercises, mobility decreasedAnxiety effect is similarIntervention?

Pain / Mood / Sleep Interaction Lorraine: Speaker by the mike Amp turned up

The Environment Stresses Increase anxiety, muscle tension, fear Provide incentives to regressContingenciesProvide a reason to recoverOr a reason not to

Pain as Behavior – Operant Conditioning Behavior rewarded is behavior repeated Behaviors not reinforced are "extinguished" It has to be that wayChanges often occur without awareness of subject or person who reinforces

Practical Implications Functional restoration may be impeded by adverse contingencies. If I get well: I’ll be abandoned I’ll have to face that jobI’ll lose my PercocetI’ll be competing with strong, young peopleI’ll lose disability income

LorraineWhat does she have to gain by recovering? What does she have to lose? Each of us has some of both. If you don’t see it, you’re missing something.

Interventions Goals Comfort FunctionRestReassuranceStrategiesTreat the painTreat the person

Multifactorial Illness / Multifactorial Treatment Education Comfort therapies Integrative medicineFitnessRestore functionNormalize mood Psychotherapy Improve coping Treat depression/anxiety Pharmacotherapy Analgesic AnxiolyticAntidepressant No Silver Bullet

Literature Review Several innovative approaches improved inpatient pain management Common elements A conviction that excellent pain management was essential to good careClose attention to patient discomfortDemonstrated commitment to patients’ comfortCollaboration / multidisciplinary team workNo single discipline was able to do it

Most Important Pay attention

Treat the Pain Pharmacotherapy Target pain, mood , anxiety, sleep

Opioids Miracle drugs in acute pain. The miracles diminish over time. Concerns : Acute Side effects Possible pain chronification Chronic Loss of efficacy Addiction

CDC Guidelines – Chronic Opioid Rx Effectiveness: “no study of opioid therapy vs placebo, no opioid, or nonopioid therapy for chronic pain evaluated long-term (≥ 1 year) outcomes related to pain, function, or quality of life. Most placebo-controlled RCTs were ≤ 6 weeks in duration. Thus , the body of evidence … is … insufficient.”US Dept HHS/Centers for Disease Control and Prevention MMWR 2016;65(1) CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

Opioids – A Few Points Effective, indispensable in acute pain Progressively less so over time. Addiction risk is minimal with short term useEven brief use may predict poor functional outcomeAddiction relapse risk is considerable ? yrs

Likelihood of Developing Opioid Use Disorder 18 mo after CNMP Onset N= 568,640 – health plan data No opioids in pre-index period No prior OUD* Opioid treatment categorized:Chronic = > 90 days Low = ≤ 36 MED*Medium = 36-120High = ≥ 120 MED If not treated with opioids, 0.004 % developed OUD Dose, duration Rates Of OUD Diagnoses OR low dose, acute 0.12% 3.03 low dose, chronic 0.72% 14.92 medium dose, acute 0.12% 2.80 medium dose, chronic 1.28% 28.69 high dose, acute 0.12% 3.10 high dose, chronic 6.1% 122.45 * opioid use disorder * MED = morphine equivalents/d Edlund MJ et al. Clin J Pain 2014;30(7):557-64 .

Chronic Opioid Treatment – the Basics Monitor outcomes closely, numerically Pain, mood, function, adverse effects Maintain accountabilityUDT, communicate with family, pharmacyMonitor PDMPAvoid concomitant addicting drugsNever continue a failed treatment

Opioid Escalation Is Age Dependent Chart review, n = 206 on long-acting opioids Starting dose ≤50 yrs old – 49 mg/d ≥ 60 yrs old – 42 mg/d Maximum dose (14-15 mo rx) Young – 452 ± 63 mg/d Old – 211 mg/d Last visit Young – 365 mg/dOld – 168 mg/d Only older patients had reduced VAS (6.9 to 5.6) Buntin-Mushock C et al. Anesth Analg. 2005;100 (6):1740-5. End VAS Morphine Equivalents Daily

LorraineWe can tell her that she’s at lower than average risk for tolerance, escalation, addiction Higher than average for constipation We should’ve seen that coming Or not coming, as it were

Multimodal Analgesia Multiple analgesics In combination Initiated pre-opContinued around-the-clock post-opWenzel JT et al. Anesthesiol Clin. 2016;34(2):287-301. Dahl JB et al. Acta Anaesthesiol Scand. 2014;58(10):1165-81. Thomas DA et al. Curr Drug Saf. 2016;11(3):196-205. Typical components:OpioidsAcetaminophen (po / IV)NSAIDs / COX-2 inhibitorsGabapentinoidsGlucocorticoidsLocal anestheticsα-2 agonists (clonidine, dexmedetomidine)Ketamine

Attack pain on multiple frontsReduces Opioid requirement Drug side effects Surgical complicationsLength of hospital stayPainWenzel JT et al. Anesthesiol Clin. 2016;34(2):287-301.Dahl JB et al. Acta Anaesthesiol Scand. 2014;58(10):1165-81.Thomas DA et al. Curr Drug Saf. 2016;11(3):196-205.From: Gorlin AW, et al. J Anaesthesiol Clin Pharmacol . 2016;32(2):160-7. LA, NSAIDs Local anesthetics Nerve endings Primary afferent DRG Descending inhibitory fibers NA, 5-HT Local anesthetics α 2 agonists Opioids, TCAs, SNRIs, α 2 agonists Dorsal horn Ascending spinothalamic fibers Opioids, ketamine, gabapentenoids Multimodal Analgesia

Lorraine By combining treatments with different mechanisms Additive effect on pain Avoids additive side effects May get by with subtherapeutic doses of single agentsMinimize GI, confusion, respiratory (sleep) effects

SNRIs – Only Chronic Pain? SNRIs are of established benefit in many chronic pains Neuropathic HeadacheMusculoskeletal / spineFibromyalgia VisceralPelvicAcute / subacute pain Less convincing, to be determined Relieve anxiety, depression, insomnia Tricyclics are SNRIs Gilron I. Drugs. 2016;76(2):159-67.

AEDs for Pain Gabapentenoids are best supported Gabapentin, pregabalin Fibromyalgia, neuropathic pain Pre-emptive analgesia in some studies Na-channel blockers less supported Except trigeminal neuralgia, headaches An update on the drug treatment of neuropathic pain. Part 2: antiepileptics and other drugs. Drug Ther Bull. 2012;50(11):126-9. PMID:23154593.

Combining Antidepressants or Anticonvulsants with Opioids Review / meta-analysis 8 trials, 1359 participants Neuropathic pain Cancer patients Compared analgesic effectiveness ±addition of adjuvants (ADs, AEDs) Results: Consistent benefit across different study designsGuan J et al. Clin J Pain. 2016;32(8):719-25 Favors experimental Favors control

Anxiolytic TCAs SNRIs NSAIDs Local anesthetics Topicals Antiarrhythmics Opioids SSRIs Benzodiazepines Bupropion β -blockers AEDs Neuroleptics? Parsimonious Polypharmacy

TENS Reduces postoperative pain and opioid side effects Lap cholecystectomySilva MB et al. Amer J Phys Med Rehabil 2012; 91: 652-7.Abdominal surgery Tokuda M et al. Clin J Pain 2014; 30: 565-70. Thoracotomy Sbruzzi G et al. Revista brasileira de cirurgia

Treat the personNot just the pain

Nursing Pilot – Lessons Learned Relationship building – honesty and trust Explain what you are doing and why Satisfaction increases when the nurse clearly considers pain control essential – even if pain was not controlled Hourly checks, asking re pain Proactive vs chasing painEducationMedications – setting realistic expectationsAnswering patients’ and families’ questions Involve patients in pain treatment, negotiateWould they like to be awakened for prns?Offer alternatives: relaxation, pulling blinds, hot/cold pack, healing services, etc. Consider other medications that may help with pain (emotional aspect) Don't give up, advocate They forgive us for not succeeding They don’t forgive us for not caring/trying

White Board Example Acceptable pain level: 2Name of pain medication: PercocetYour next dose is due at: 10 am PRN pain medication available? YesShould I wake you? Yes

Making Pain a Priority QI pilot of NS patients, N = 96 Attention to documentation of periop painStandardized analgesiaOpioid, APAP, ketamine, gabapentin Increased nursing assessment Maximize prn doses before calling for uncontrolled pain Goal: “6 must be fixed” (always intervene for pain ≥ 6/10)32% pain reduction in 1st POD for all neurosurgical patients43% reduction among spinal surgery patientsTitsworth WL et al. J Neurosurg. 2016 Mar 11:1-10. [Epub]

Assess Often Categorical: None – mild – moderate – severe Numerical Rating Scale: 0-10 Many studies of pain assessment tools excluded patients who had difficulties using them. Faces: for children PAINAD Malara A et al. J Alzheimers Dis.2016;50(4):1217-25. Difficult to quantify an inherently subjective experience. See Catanantia & Gambassia, Surgical Oncology 2010; 19, 140-148.

Elderly / Demented Require Special Attention Historically overlooked, undertreated Factors: AttitudesCognitive impairmentCommunication deficitsRecent focus of attention≥ 15 behavioral assessment scales developedMost use similar indicators Facial expressions Verbalizations Non-verbal vocalizationsMovements Mood changes Changes in activity patternsJosé Closs S. J Clin Nurs. 2008;17(8):1110-2

PAINAD Pain Assessment in Advanced Dementia Scale Items* 0 1 2 Score Breathing independent of vocalization Normal Occasional labored breathing. Short period of hyperventilation. Noisy labored breathing. Long period of hyperventilation. Cheyne-Stokes respirations.   Negative vocalization None Occasional moan or groan. Low- level speech with a negative or disapproving quality. Repeated troubled calling out. Loud moaning or groaning. Crying.   Facial expression Smiling or inexpressive Sad. Frightened. Frown. Facial grimacing.   Body language Relaxed Tense. Distressed pacing. Fidgeting. Rigid. Fists clenched. Knees pulled up. Pulling or pushing away. Striking out.   Consolabllity No need to console Distracted or reassured by voice or touch. Unable to console, distract or reassure   Total   Warden V et al. J Am Med Dir Assoc. 2003;4:9-15.

Education for Patient and Family Prolonged dysfunction often results from faulty beliefs, information As does family mismanagement Uncertainty, misconceptions increase pain, debilityTeach: Physiology of the pain What the pain means – and doesn’t mean How long should it last? Distinguish hurt from harm What can be done about it?

It’s Not My Job

Fitness – Psychotherapy in Disguise Benefit documented Unipolar depression Chronic fatigueCounteracts learned helplessnessDecreases fear of injuryGives realistic hopeRestores access to lost gratification

Address Depression, Anxiety “How is all this affecting you?” “You seem glum today.” “You look scared – are you concerned about anything?”

Integrative Medicine Bodywork Manipulative and body-based therapies Massage, craniosacral, reflexology Mind–body Mind–body Guided imagery , relaxation, music, Qi Gong Energy medicine Healing touch , Reiki, Energy therapies Chinese Medicine Acupuncture, acupressureNIH review: Nahin RL et al. Mayo Clin Proc. 2016;91(9):1292-306.

Complementary Health Studies Evidence for Selected Approaches by Type of Pain Approach Back pain Fibromyalgia Knee OA Neck pain HA / migraine Acupuncture 2 Positive 2 Positive 1 Positive Massage therapy 3 Positive, 1 negative 2 Positive 3 Positive Relaxation approaches 4 Positive 4 Positive Spinal manipulation 4 Positive, 3 negative Osteopathic manipulation 2 Positive, 2 negative Tai chi 1 Positive Yoga 4 Positive 1 Positive Nahin RL et al. Mayo Clin Proc. 2016;91(9):1292-306

Mind–body Therapies Focus on interactions between brain, mind, body and behavior Meditation, relaxation, hypnotherapy, yoga, Tai Chi, music therapy, qigong, guided imagery. GoalsReduce anxiety, fear, anger, depression, pain Sense of emotional, physical and spiritual wellbeing. Systematic reviews and meta-analysesConsistent results Reduced anxiety and stress Improved sleep Better overall quality of lifeMindfulness-based stress reduction is the best studied Deng & Cassileth Nature Reviews. Clinical Oncology 2013; 10, 656–664.

Mindfulness Meditation Stimulus intensity 3 days training 20 min/d High vs low pain stimulus Reading vs math task vs meditation Zeidan F et al. J Pain 2010;11(3):199-209

BFT in Chronic Pain Electronic monitors provide feedback (e.g. audible) re body function Skin temp, sweating, EMG, HR Patients learn to modify functionMost research is old, weakReview Usually as effective as other relaxation strategies Headache - 60 studies, 2,445 patients, efficacy ~ propranolol Musculoskeletal pain - almost as effective as for headache Neuropathic pain - unclear GI pain - effective for IBS Changes patient's view of symptom and its meaning DeGood DE, APS Bulletin 3(3), 1993

Hypnosis in Geriatric Inpatients Massage Hypnosis Month BPI General Pain Hypnosis Massage Massage Hypnosis Month BPI General Pain Hypnosis Massage RCT Hypnosis vs massage N = 53 Mean age : 80.6 Chronic pain with impact on daily activities , intensity   >4/10 Adapted analgesic treatment No cognitive impairment. Brief pain inventory Pain decreased in both groups after each session Average pain decreased more with hypnosis Depression improved significantly only in the hypnosis group (P = 0.049). No effect in either group 3 months post discharge. Ardigo S et al. BMC Geriatrics 2016; 16(1): 1-8

Pre-CABG Hypnosis Double-blind , RCTN = 44 CABG patientsPre-op hypnosis vs information – day of surgery Results Lower anxiety (STA-I) and depression (BDI) with hypnotherapy Less remifentanil ( ↓ 32%) and morphine (↓ 64%) Vent time shorter (↓ 24% – 6.8 vs. 8.9 hrs) Akgul A et al, Thorac Cardiovasc Surg. 2016 Apr 4. [Epub ahead of print]

CBT in Depressed Orthopedic Inpatients N = 84 with CLBP and depressive symptoms Inpatient orthopedic rehabilitation Standard program includes 4 hrs group cognitive behavioral pain management 6 group sessions of progressive muscle relaxationRandomized to supplemental CBT for depressionAssessed depression, anxiety, somatization, sick leave Benefit for mood and anxiety persisted at 24-months Days of sick leave decreased at 6 months. Hampel &  Tlach . J Back Musculoskelet Rehabil. 2015;28(1):49-60.

Massage Efficacy Documented Post-op pain Meta-analysis 12 high quality, 4 low quality studiesBoyd C et al, Pain Med. 2016;17(9):1757-72 Cancer Pain Meta-Analysis12 studiesLee SH et al. Integr Cancer Ther . 2015;14(4):297-304.

Healing Touch Acute care inpatients Reductions in pain, anxiety, and LOSLincoln V et al. Holistic Nursing Practice 2014; 28(3):164-170.Postop outpatients Reduced pain, anxiety Foley MK et al. J Holist Nurs . 2016;34(3):271-9 Post TKA inpatients Reduced pain, anxiety Hardwick ME et al. Orthop Nurs. 2012;31(1):5-11

Healing Touch Controlled inpatient study 41 TKA patients HT daily, starting in PACUHardwick ME et al. Orthop Nurs. 2012;31(1 ):5-11. Anxiety Pain State-Trait Anxiety Index Pain VAS control HT control HT

Does Lorraine Need Soothing? Massage helps fibromyalgia, some postop pain Touch soothes Our mothers knew that

Yoga Metaanalysis of 10 RCTs Yoga (positions, meditation, breathing exercises) Improved anxiety, depression, stress, perceived overall health Lin KY et al. Evid. Based Complement. Alternat . Med. 2011; 2011: 659876 Systematic review 10 studies, 6 RCTs Breast cancer was the most common diagnosisVariable study quality, mostly adequate Some positive results, but variability and quality preclude conclusions re efficacy for cancer-related symptoms. Smith & Pukall CF. Psychooncology 2009; 18:465–475.

Yoga Review of studies of yoga in multiple conditions Consistent improvement in pain, function, cognition Often comparable benefit to tai chi, other forms of exerciseField T. Complement Ther Clin Pract. 2016;24:145-61.Chronic Low Back Pain Systematic review, 14 studies Consistent evidence of reduced pain and disability Self-efficacy and hours of exercise may be the most important factors Unlike PT, not limited by time, insurance Chang DG et al. J Orthop Rheumatol. 2016;3(1):1-8.

Aromatherapy in Burn Pain Single-blind, N = 90 patients Burns <20%3 groupsAromatherapy massageInhalation aromatherapyControl Assessed 10 min after intervention Seyyed-Rasooli A et al. Burns. 2016; pii : S0305-4179(16)30186-3 . Pain

Operant - Remind Families / Staff Help can harm Enabling Patients regressHelpPatients progressIgnore maladaptive behaviors Not maladaptive people Use the carrot, not the stick

What Can We Do For Ralph? There is considerable literature re how families affect pain patients. There is a little literature on how pain patients affect families. There is almost none on what to do about that.So I used my own strategies – from our chronic pain rehabilitation program.

She says she was trying acupuncture in an attempt to relieve his chronic headaches.

The Impact of Chronic Pain on the Family Losses Money Social activitiesRecreation Life changesRole reversalWork/career Emotions Anger, resentment Guilt, self blame Fear Future Disease outcomes SurvivalFrom: West C et al. J Clin Nurs. 2012;21(23-24):3352-60

Recommendations for Families of CNCP Patients Do Don’t Support, validate Reject, challenge sxs Ignore pain behaviors Ignore person, c riticize pain behavior Encourage activities Warn against them Be a playmate, friend, lover Be a nurse, aide, mother

Ralph and Lorraine Both need to know clearly: What things will hurt What things will harmFew things are as toxic in chronic pain as rest

Teach Ralph about Feeding Cows and O2 Masks Families, without thinking, may assume that they are capable of eternal giving without any getting. If they are to be useful to the person with pain, they must get their own needs met in some way. Oth­erwise, they become cauldrons of resentment.

Special Challenges Pain in patients with substance use disorder Acute on chronic pain High dose opioid / benzodiazepine wean

Substance Use Disorder The 3 C’s Inability to reliably Control useContinued use despite adverse Consequences C raving/ Compulsive use Present in iatrogenic addiction as well as recreational addiction But the appearance is different I’ll describe the recreational addict You describe the iatrogenic addict

Addiction and theBrain Anti-reward System Koob GF, LeMoal M. Ann Rev Psychol 2008;59:29-53. Struggling less to get high t han to feel normal

Pain + Patient in Recovery Likely opioid tolerant or will rapidly re-develop it Requires more analgesia than others, not less Transition ASAP to least euphorigenic drugOralLong actingTramadol, etcNot IV hydromorphone Redouble sobriety work Notify sponsor Have responsible opioid manager on discharge

Iatrogenic Relapse A recovering chronic pain patient started dating a newly recovering man with heroin addiction Both worked a good sobriety program, stayed sober for a year Boyfriend went for colonoscopy IV Demerol and Versed Cravings triggered Went home, took heroin, to which he was no longer tolerant Dose was fatal

Pain + Active Addiction Similar principles, more conflict With both, optimize multimodal analgesia and nonpharmacological treatments May be undertreated due to staff attitudes, perceived manipulativenessObjective signsA patient loudly demanding analgesia is not overdosed A patient drifting off is not undermedicated Consider buprenorphine, methadone

Chronic Pain + Substance Use Disorder Avoid addicting substances when possible Its usually possible Maximize safer strategies – meds, fitness, psychotherapy Withhold chronic opioids/benzodiazepines from those unwilling to participate in recovery work, treatmentWhen unavoidable:Maximum accountability (UDT, pill counts, family talks)Buprenorphine probably bestEnforce contract – 1 provider, no early refills

Walter 58 y.o ., severe peripheral vascular disease, s/p left AKALeft phantom pain + stump neuromaRight leg ischemic pain, ischemic neuropathy Not responsive to a variety of adjuvants Brief relief with nerve blocks Recurrent infections preclude cord stimulation Severe functional impairment Severe alcoholism, unwilling to consider sobrietyDepressed

Walter Decision to treat as “terminal pain” Methadone titrated to 160 mg/d with good relief After 5 years, dose had increased to 240 mg/dResumed socialization Got a girl friend and part time “job” Still no sobriety program, drinks only if out of methadone No further surgeries, except carotid endarterectomy Considers his quality of life excellent

Acute on Chronic Pain N = 92 general medical inpatients Those with acute on chronic painHad more time in severe pain (60% vs 17%)Had more consecutive days in severe pain (65% vs 20%) Chronic opioid users More risk of undertreatment More risk of opioid overdose Lin RJ et al. Am J Hospice & Pall Med 2016; 33(1 ):16-19 . Strategy – maximize multimodal analgesiaTENSRelaxation therapies / massageKetamineRegional anesthesia

The Therapeutic Window Closes Time Opioid dose Opioid tolerant patients after painful surgery (e.g. lumbar fusion) May have no therapeutic window As IV opioids are given, pain remains 9/10 to the point of coma Therapeutic dose = toxic dose Lethal dose Analgesic dose Hypothetical Graph

Ketamine Supplementation in Post-op Pain Analgesic Opioid sparing May be especially useful in opioid tolerant patientsPossibly most effective in those with highest pain levelsReduces persistent postop painGorlin AW et al. J Anaesthesiol Clin Pharmacol. 2016;32(2):160-7 . Barreveld AM et al. Pain Med. 2013;14(6):925-34.McNicol ED et al. Acta Anaesthesiol Scand. 2014;58(10):1199-213

Conclusions Pain is a biopsychosocial condition It requires multifactorial treatment Rarely can one person / discipline / treatment optimize outcomeSuccess comes from addressing the whole personNociceptionKnowledge, fearPsychological symptomsSleep Stress Contingencies Family

Slides in case audience wants to talk about weaning / detoxification

2 types require interventionOpioid Sedative Includes alcohol, baclofen, carisoprodol Other substances are minor issuesStimulants, nicotine, cannabis, ergot, antiepilepticsSSRIs, SNRIs may require long (months) taper Strategies for weaningMore like swapping recipes than reporting science Virtually no controlled studies Weaning Dependency Producing Substances

Most withdrawal signs / symptoms have the appearance of opponent processes that continue in the absence of the drug. Stimulant withdrawal – lethargy AED withdrawal – seizures Sedative withdrawal – agitation Opioid withdrawal – hyperalgesia, diarrheaWithdrawal

Establish baselineOpioidsSedatives It costs nothing to be generous Dose reduction There are numerous ways to do itNone is demonstrably superiorFishbain DA et al. Annals of Clinical Psychiatry 5:53-65, 1993Plunkett A et al. Pain Management 2013; 3(4), 277-284. Treatment of protracted / postacute withdrawal Most addiction relapse is in 1 st 3 months This is when protracted withdrawal is maximal It is preventable3 Phases of Weaning

Drugs to avoid:Very short acting – highs and lows uncomfortable, unsafe Drugs that accumulate Patient discharged with significant blood level Withdraws at homeCrashes, relapses Combined respiratory depressantse.g., phenobarbital + methadoneDetoxification Techniques

Small pupils Quiet abdomen Slow respiration Mydriasis Diaphoresis Piloerection GI ↑ activity Yawning NystagmusAtaxiaSlow respiration ±HyperreflexiaSeizure Delirium Can be lethal Opioid vs. Sedative − Distinguishing Signs Toxicity Withdrawal Opioid Sedative

Varies with comorbid conditions, nature of dependence, agent, location. Inpatient alcohol detox may only require 2 doses of diazepam. Day care pain patients usually require 12-14 days (hyperalgesia) Doubled / tripled time for outpatients. Rate of Wean

Drug Options for Weaning Opioids All full µ agonists are effective and legal Kinetics and costs are the main issues 12 or 24-hour morphine is effective, comfortable Adjuvants ClonidineLoperamideSedatives Benzodiazepines (lorazepam, chlordiazepoxide, diazepam ) Adjuvants Gabapentenoids Valproate, carbamazepine Other antiepileptic drugs

Inpatient @ 25%/d Days Required to Wean Daily Morphine Equivalents Outpatient @ 20% q4d Rates of Opioid Wean

Some patients rapidly, comfortably withdrawSpeed up the process Others have extreme symptoms, protracted course Generous adjuvants Slow downGenerous anxiolysis, sedation, nausea controlTCAs, trazodoneAntiepilepticsAtypical neuroleptics Rigid Protocols Are Inadequate

Adjuvant Drugs for Opioid Wean Trazodone Pozzi G et al. Drug Alcohol Depend. 2000;59(3):287-94Doxepin Dufficy RG. Milit Med 138:748, 1973Spensley J. Int J Addict. 1976;11(1):191-7 Gabapentin Freye E, Levy JV, Partecke L. Neurophysiol Clin. 2004;34(2):81-9.Quetiapine Pinkofsky HB et al. J Clin Psychiatry. 2005;66(10):1285-8Anti-emeticsSleepTrazodoneMirtazapine

ExerciseBiofeedback / imagery Meditation Yoga Non-Pharmacological Adjuvants